WO2011152543A1 - Excitations des modes de cavité optique dans des microparticules magnétiques fluorescentes - Google Patents

Excitations des modes de cavité optique dans des microparticules magnétiques fluorescentes Download PDF

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Publication number
WO2011152543A1
WO2011152543A1 PCT/JP2011/062859 JP2011062859W WO2011152543A1 WO 2011152543 A1 WO2011152543 A1 WO 2011152543A1 JP 2011062859 W JP2011062859 W JP 2011062859W WO 2011152543 A1 WO2011152543 A1 WO 2011152543A1
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microcavity
optical
optical cavity
fluorescent material
microcavities
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PCT/JP2011/062859
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English (en)
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Michael Himmelhaus
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Fujirebio Inc.
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Priority to EP11789943.5A priority Critical patent/EP2577276A4/fr
Priority to JP2012554140A priority patent/JP2013527428A/ja
Priority to US13/701,209 priority patent/US20130105709A1/en
Publication of WO2011152543A1 publication Critical patent/WO2011152543A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
    • G—PHYSICS
    • G02—OPTICS
    • G02F—OPTICAL DEVICES OR ARRANGEMENTS FOR THE CONTROL OF LIGHT BY MODIFICATION OF THE OPTICAL PROPERTIES OF THE MEDIA OF THE ELEMENTS INVOLVED THEREIN; NON-LINEAR OPTICS; FREQUENCY-CHANGING OF LIGHT; OPTICAL LOGIC ELEMENTS; OPTICAL ANALOGUE/DIGITAL CONVERTERS
    • G02F1/00—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics
    • G02F1/01—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour 
    • G02F1/09—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour  based on magneto-optical elements, e.g. exhibiting Faraday effect

Definitions

  • Optical microcavities have been successfully applied to a variety of applications in optics, such as miniature laser sources (J. L. Jewell et al., Appl. Phys. Lett. Vol.54, pp.1400ff., 1989; M. Kuwata-Gonokami et al., Jpn. J. Appl. Phys. (Part 2) Vol.31, pp. L99ff., 1992; S. M. Spillane et al., Nature (London) Vol.415, pp.621ff., 2002; V. N. Astratov et al., Appl. Phys. Lett. Vol.85, pp.5508ff., 2004), optical waveguides (V.
  • WGMs whispering gallery modes
  • WO 02/13337A1 WO 02/01 147A1 , US 2003/0206693A1 , US2005/022153A1 , and WO 2004/038349A1 .
  • metal-coated or metal-decorated cavities can be utilized.
  • WO 02/071 13A1 , WO 01 /15288 A1 , US 2004/0150818A1 , and US 2003/0218744A1 describe the use of metal particles, metal particle
  • the metal particles/films may further bear a fluorescent material, such as a laser dye.
  • WO2007129682 describes the use of fluorescent dielectric microcavities encapsulated into a metallic coating for biosensing applications.
  • Magnetic particles and composites thereof for applications in catalysis, environmental remediation, microfluidics, cell separation, immunomagnetic separation and related applications in the biomedical field and (bio-) sensing have been developed in recent years in numerous types in nanometer to micrometer dimensions and with a variety of surface functionalizations (L. Stanciu et al., Sensors Vol. 9, pp. 2976-2999, 2009; C. Liu et al. , J . Appl. Phys. Vol. 105, pp. 1 02014/1 -1 1 , 2009; N . Jaffreciz-Renault, Sensors Vol. 7, pp. 589-614, 2007; N . Pamme, Lab Chip Vol. 6, pp. 24-38, 2006).
  • the particles are hybrid particles consisting of nano-sized magnetic particles embedded into a polymeric or inorganic matrix material with an aim to improve stability of the colloidal suspension in view of particle
  • fluorescent magnetic particles have been fabricated, for example by embedding a fluorescent dye into the polymer matrix of a hybrid particle, and even have become commercially available (e.g. , Compel magnetic fluorescent microspheres, Bangs Laboratories, Inc. , Fisher, IN).
  • the present invention has been achieved in order to solve problems the above mentioned arts.
  • an optical cavity mode apparatus comprises at least one microcavity having magnetism; a light source for supplying light irradiation to the microcavity; an optical apparatus for detection of optical cavity modes of the microcavity; and a magnetic controller for magnetically controlling position of the microcavity.
  • a method for sensing a target object using optical mode excitations in at least one microcavity comprises the steps of: preparing the microcavity having magnetism; exciting the microcavity by irradiation of a light source to obtain spectra of the microcavity; detecting at least one optical cavity mode of the microcavity stimulated by the light source, wherein the position of the microcavity is controlled by a magnetic controller.
  • a method for sensing a target object using optical mode excitations in at least one microcavity comprising the steps of: preparing the microcavity having magnetism; exciting the microcavity by irradiation of a light source to obtain spectra of the microcavity; detecting at least one optical cavity modes of the microcavity stimulated by the light source, wherein the microcavity interacts with magnetized material.
  • Fig. 1 shows a microcavity or a cluster as an aggregate of microcavities optionally containing a fluorescent material for excitation of optical cavity modes in the microcavity or cluster of microcavities: (a) a single microcavity without a coating; (b) a single microcavity with a coating for achievement of wanted optical properties; (c) a cluster as an aggregate of microcavities without a coating; a cluster as an aggregate of microcavities which are coated in either such a way that (d) each cavity is individually coated or (e) in such a way that neighboring cavities form optical contacts with each other.
  • Fig. 2 shows two basic schemes of hybrid particles containing a magnetizable material, wherein in scheme (I) the magnetizable material 2 is distributed over the core 1 of the hybrid particle and in scheme (I I) the magnetizable material 2 is a coating of the core 1 ; the outer coating 3 is optional.
  • Fig. 3 compares the normalized optical transmission 1 of an aqueous suspension of 8 ⁇ polystyrene beads containing magnetite with the excitation laser position 2 and the fluorescence emission 3 of Nile Red as chosen for Examples 2 and 3.
  • Fig. 4 shows an experimental set-up for preparation of fluorescent paramagnetic beads.
  • Fig. 5 shows fluorescence emission spectra of Bangs Compel magnetic microbeads with a nominal diameter of 8 ⁇ either doped with Nile Red (a) or non-doped, i.e. not containing any fluorescent dye, (b).
  • CCD Charge-coupled device
  • PBS Phosphate buffered saline
  • Reflection and transmission at a surface In general, the surface of a material has the ability to reflect a fraction of impinging light back into its ambient, while another fraction is transmitted into the material, where it may be absorbed in the course of its travel.
  • the power ratio of reflected light to incident light the "Reflectivity” or “Reflectance”, R, of the ambient/material interface (or material/ambient interface). Accordingly, the power ratio of transmitted light to incident light is called the
  • Transmittance T
  • R and T both are properties of the interface, i.e. their values depend on the optical properties of both, the material and its ambient. Further, they depend on the angle of incidence and the polarization of the light impinging onto this interface. Both R and T can be calculated by means of the Fresnel equations for reflection and transmission. The same terminology can be also applied to the total reflection and total transmission of a stratified sequence of interfaces.
  • An optical cavity is a closed volume confined by a closed boundary area (the "surface" of the cavity), which is highly reflective to light in the ultraviolet (UV) , visible (vis) and/or infrared (I R) region of the electromagnetic spectrum .
  • the reflectance of this boundary area may also be dependent on the incidence angle of the light impinging on the boundary area with respect to the local surface normal. Further, the reflectance may depend on the location , i.e. where the lig ht impinges onto the boundary area.
  • the inner volume of the optical cavity may consist of vacuum , air, or any material that shows h ig h transmission in the UV, visible , and/or I R.
  • An optical cavity may be coated with a material different from the material of which the optical cavity is made.
  • the material used for coating may have, e.g . , different optical properties, such as different refractive index or absorption coefficient. Fu rther it may comprise different physical, chemical, or biochemical properties than the material of the optical cavity, such as different mechanical strength , chemical inertness or reactivity, and/or antifouling or related biofunctional functionality.
  • this optional coating is referred to as "shell", while the optical cavity is called "core".
  • the total system i.e.
  • (optical) microresonator a part of the su rface of the microresonator may be coated with additional layers (e.g . on top of the shell) as a part of the sensing process, for example to provide a suitable biofunctional interface for detection of specific binding events or in the course of the sensing process when target molecu les adsorb on the microresonator su rface or a part of it.
  • An optical cavity is characterized by two parameters: First, its volume V, and second , its quality factor Q.
  • an optical cavity may be characterized in terms of the free spectral range(s) ⁇ TM and the bandwidth(s) A m of its optical cavity modes (for definitions see below).
  • the term "optical cavity” (“microresonator”) refers to those optical cavities (microresonators) with a quality factor Q > 1 .
  • the light stored in the microresonator may be stored in the optical cavity solely, e.g . when using a highly reflective metal shell, or it may also penetrate into the shell , e.g. when using a dielectric or semiconducting shell. Therefore, it depends on the particular system under consideration, which terms (volume and Q- factor of the optical cavity or those of the microresonator) are more suitable to characterize the resulting optical properties of the microresonator.
  • Quality factor The quality factor (or "Q-factor") of an optical cavity is a measure of its potential to trap photons inside of the cavity. It is defined as
  • volume of an optical cavity The volume of an optical cavity is defined as its inner geometrical volume, which is confined by the surface of the cavity, i.e. the reflective boundary area.
  • the free spectral range (FS ) ⁇ of an optical system refers to the spacing between its optical modes.
  • Ambient (environment) of an optical cavity or microresonator The "ambient” or “environment” of an optical cavity or microresonator is that volume enclosing the cavity (microresonator), which is neither part of the optical cavity, nor of its optional shell (in the case of a microresonator).
  • the highly reflective surface of the optical cavity (or microresonator) is not part of its ambient. It must be noted that in practice, the highly reflective surface of the optical cavity (microresonator) has a finite thickness, which is not part of the ambient. The same holds for the optional shell , which has also a finite th ickness and does not belong to the microresonator's ambient.
  • the ambient or environment of an optical cavity may comprise entirely different physical and chemical properties from that of the cavity (microresonator), in particu lar different optical , mechanical, electrical, and (bio-)chemical properties. For example, it may strongly absorb in the electromag netic region , in which the optical cavity (microresonator) is operated .
  • the ambient may be heterogeneous.
  • the extension to wh ich the enclosing volume is considered as ambient, depends on the application . I n the case of a microresonator broug ht into a microfluidic device, it may be the microfluid ic channel.
  • the ambient it is that part of the enclosing volume of the optical cavity or microresonator, which is of relevance for the optical cavity's (microresonator's) operation , for example in terms of its impact on the optical cavity modes of the cavity (microresonator) in view of their properties, excitation , and/or detection .
  • Optical cavity mode An optical cavity mode or just “cavity mode” is a wave solution of the electromagnetic field equations (Maxwell equations) for a given cavity. Different modes may have d ifferent directions of propagation depending on geometry and optical properties of the cavity. These modes are discrete and can be numbered with an integer m, the so-called “mode number”, d ue to the restrictive boundary conditions at the cavity surface.
  • the electromagnetic spectrum in the presence of the cavity can be divided into allowed and forbidden zones.
  • the complete solution of the Maxwell equations consists of internal and external electromagnetic fields inside and outside of the cavity, respectively.
  • the term "cavity mode" refers to the inner electromagnetic fields inside the cavity (within the cavity volume as defined above) unless otherwise stated .
  • the wave solutions depend on the shape and volume of the cavity as well as on the reflectance of the bou ndary area, i .e. the cavity surface.
  • the full set of solutions of Maxwell's equations comprises also the fields outside of the optical cavity (microresonator) , i.e. in the cavity's
  • evanescent fields may show some leakage, i.e. propagation of photons out of the evanescent field into the far field of the optical cavity, i.e. far beyond the extension of the evanescent field into the ambient.
  • Such waves are caused, for example, by scattering of photons at imperfections or other kinds of causes, which are typically not accounted for in the theoretical description, since the latter typically assumes smooth interfaces and boundary layers.
  • Such stray light effects are not considered in the following , i.e. do not hamper the
  • evanescent field character of an ideally evanescent field In the same way, evanescent field tunneling across a nanometer-sized gap into a medium, in which wave propagation is then allowed, does not hamper the evanescent field character of the evanescent field.
  • n is an integer and is also used for numbering of the modes, i.e. , as their mode number, R is the sphere radius, and n ca is the refractive index inside of the cavity.
  • cavity mode m will be used synonymously with the term
  • the "dimension” or “size” of an optical cavity or microresonator is a measure for is spatial extension. For a spherical optical cavity or microresonator, it is its diameter, for an ellipsoidal optical cavity or microresonator, it is the length of its largest principal axis. For an optical cavity or microresonator of arbitrary shape, the dimension (size) is given by the diameter of the smallest sphere that can fully engulf the optical cavity or microresonator.
  • optical microcavitv In the following , an optical cavity or microresonator will be called “optical microcavity”, if it has a dimension of below one millimeter. Accordingly, a cluster of optical cavities or microresonators will be called a “cluster of optical microcavities”, if the dimension of at least one of the constituting optical cavities or microresonators is below one millimeter.
  • microcavities or clusters of microcavities may be part of a more complex optical system comprising also other kinds of optical elements than microcavities or clusters of microcavities as defined above. Also such more complex systems will be called “microcavity” or “cluster of microcavities” in the following, depending on which of the two systems they preferentially contain .
  • Magnetic optical microcavity An optical microcavity or cluster of optical microcavities is called “magnetic” if the optical microcavity or at least on of the optical cavities or microresonators constituting the cluster of optical microcavities can interact with magnetic materials via magnetic forces.
  • Mode coupling We define mode coupling as the interaction between cavity modes emitted by two or more microresonators that are positioned in contact with each other or in close vicinity to allow an optical contact. This phenomenon has been pointed out by S. Deng et al. (Opt. Express Vol. 12, pp. 6468-6480, 2004), who have performed simulations on mode guiding through a series of microspheres. The same phenomenon has been experimentally demonstrated by V. N. Astratov et al. (Appl. Phys. Lett. Vol. 83, pp.
  • Optical contact Two microresonators are said to have an "optical contact", if light can transmit from one resonator to the other one and vice versa . In this sense, an optical contact allows potentially for mode coupling between two resonators in the sense defined above. Accord ingly, a microresonator has an optical contact with the substrate if it may exchange light with it.
  • a cluster is defined as an aggregate of cavities (microresonators) which may be either in 2 or 3 dimensions (cf. Fig. 1 (c)-(e)).
  • the individual cavities (microresonators) are either positioned in such way that they are in contact with each other or in close vicinity in order to promote the superposition of their cavity mode spectra and/or cavity mode coupling . They may be attached to a surface or float freely in a liquid medium. Further, they may be - at least temporally - detached from a surface.
  • the individual cavities may be coated as described above in either such a way that each cavity is individually coated (Fig. 1 (d)) or in such a way that neig hboring cavities within a cluster form optical contacts with each other (Fig .
  • the cluster may be formed randomly or in an ordered fashion for example using micromanipulation techniques, micropatterning and/or self-assembly. Further, the cluster may be formed in the course of a sensing process, for example inside of a medium, such as a live cell, after penetration of cavities (microresonators) into the med ium to facilitate sensing of the wanted physical, chemical, biochemical, and/or biomechanical property. Also, combinations of all schemes shown in Fig . 1 are feasible. In general, the clusters of particles can be distributed over the surface in a random or an ordered fashion , which may be either in two- or in th ree- dimensional structures. Thereby, photonic crystals may be formed .
  • Lasing threshold The threshold for stimulated emission of a microresonator (optical cavity) , also called the “lasing threshold”, is defined as the optical pump power of the microresonator where the light amplification via stimulated emission just compensates the losses occurring during propagation of the corresponding light ray within the microresonator. Since the losses for light rays traveling within a cavity mode are lower than for light rays that do not match a cavity mode, the cavity modes exhibit typically the lowest lasing thresholds (which may still differ from each other depending on the actual losses of the respective modes) of all potential optical excitations of a microresonator. I n practice, the lasing threshold can be determined by monitoring the optical output power of the microresonator (e.g .
  • the slope of th is dependence is (significantly) higher above than below the lasing threshold so that the lasing threshold can be determined from the intersection of these two dependencies (cf. for example A. Francois, M . H immelhaus, Appl. Phys. Lett. Vol. 94, 031 1 01 , 2009) .
  • the lasing threshold When talking about the "lasing th reshold of an optical microresonator", one typically refers to the lasing threshold of that optical cavity mode with the lowest threshold within the observed (utilized) spectral range.
  • the "lasing threshold of a cluster of optical microresonators” may be envisioned as the lasing threshold of that optical cavity mode generated in the cluster (by any of its constituting microresonators and/or any combination(s) thereof) with the lowest th reshold within the observed (utilized) spectral range.
  • Optical microresonators and clusters of the microresonators have been shown to be promising tools for the development of optical sensors of small dimension with the dependency of their cavity mode excitations on external parameters, which influence their immediate environment, as the transducer mechan ism.
  • One major advantage of the application of small sensors, e .g . in the sub-millimeter regime, would be to allow hig hly localized sensing of the physical and/or (bio-) chemical cond ition of the target.
  • physical and/or (bio-) chemical quantities of interest such as refractive index, temperature, pressure, flow velocity, turbidity, and analyte concentration
  • Such information would be very valuable in view of the further optimization of such systems with regard to the speed and accuracy of their performance and the total yield , e.g. , in the case of a microfluidic synthesis process.
  • optical cavity mode sensors can be incorporated by live cells and be used for the measurement of biomechanical forces during endocytosis (U.S. provisional patent application No. 61 /1 1 1 ,369 filed on November 7, 2008; A. Francois and M . Himmelhaus, Biosens. Bioelectron. Vol. 25, pp. 418-427, 2009). This became merely possible because the total sensor size was reduced to a dimension below the size limit for phagocytosis of the cell line used.
  • Polymer latex beads such as polystyrene (PS) microspheres
  • PS polystyrene
  • the particles typically bear a suitable (bio-)functional coating, which allows for subsequent specific functionalization, e.g. , decoration of the beads' surface with specific antibodies and other kinds of specifically binding proteins.
  • Fig. 2 Examples of particle architectures of magnetizable polymer particles are sketched in Fig. 2.
  • the material used for magnetization 2 can be either distributed throughout the polymer core 1 of the particle as shown in Fig. 2(l) or encapsulate the core 1 as shown in Fig. 2(H).
  • magnetizable material 2 is typically inorganic, while core 1 and outer coating 3 are typically organic materials, these kinds of particles are often referred to as “hybrid particles".
  • the coating 3 is optional and may be omitted.
  • the magnetizable material may be coated individually, e.g. crystallite by crystallite, e.g . , for the purpose of protection and (bio-)functionalization.
  • intricacies which do not alter the basic principles, will be omitted.
  • the fluorescent material can either be incorporated in the core 1 or in the outer coating 3 of the particle. It can also be attached onto the surface of the coating 3. Further, fluorescent and magnetic properties can be combined , e.g . by application of doped QDs, which are magnetic and fluorescent at the same time (D . Magana et al . , J . Am. Chem. Soc. Vol. 1 28, pp. 2931 -2939, 2006; L. Besombes et al. , Acta Phys. Polonica A, Vol. 1 08, pp. 527-540) .
  • the QDs would additionally take the role of the magnetizable material 2 in Fig . 2, i .e. they may be d istributed across the core 1 of the particle or form a shell around the core 1 .
  • the magnetizable QDs, i.e. , the magnetizable material 2 may be also incorporated into the outer coating 3 or attached to it.
  • optical cavity modes such as WGMs (A. Weller et al. , Appl. Phys. B Vol. 90, pp. 561 -567, 2008) or FPMs (A. Weller and M . H immelhaus, Appl . Phys. Lett. Vol. 89, pp . 241 1 05/1 -3, 2006)
  • WGMs A. Weller et al. , Appl. Phys. B Vol. 90, pp. 561 -567, 2008
  • FPMs A. Weller and M . H immelhaus, Appl . Phys. Lett. Vol. 89, pp . 241 1 05/1 -3, 2006
  • the refractive index of the core without magnetizable material would be around 1 .59, while optical absorption within the visible regime is basically negligible.
  • Iron oxide derivatives such as magnetite and hematite, which are most commonly used in the fabrication of commercially available superparamagnetic particles, have typically high refractive indices (e.g. , magnetite ⁇ 2.42, hematite ⁇ 2.87- 3.22) and, as already mentioned above, show significant optical absorption in the visible regime (J. Wang et al. , J . Am. Ceram. Soc. Vol. 88, pp. 3449- 3454, 2005; M .
  • the inventor of the present invention realized that the a priori presumed obstruction of optical cavity mode excitation in magnetic hybrid particles can be overcome in d ifferent ways.
  • magnetic materials come in many different colors, depend ing on chemical composition , crystal structu re, and particle size and shape (cf. , e.g . , Wang et al. , J . Am. Chem. Soc. Vol. 88, pp. 3449-3454, 2005) .
  • Fig . 3 displays the optical transmittance of a colloidal suspension of mag netite-doped polystyrene beads, i.e. the beads used in the Examples 2 and 3. While the bead suspension shows a distinct brownish color indicating the presence of the magnetite, the transmission spectrum 1 of the colloidal suspension reveals that there is a window of relatively hig h transmission between 51 0 and 675 nm. Thus, with N ile Red as fluorescent dye ⁇ cf. emission spectrum 3 in Fig .
  • the structure of the hybrid particles may be exploited to overcome the limitations of optical cavity mode excitations in their interior. As becomes obvious from the example structures shown in Fig .
  • the magnetic material does not occupy the entire particle volume. Therefore, depending on the kind of optical cavity mode excitation , just those parts of the particle may be chosen for their excitation and propagation , which avoid the mag netizable material. It is well known , for example, that WGMs travel very close to the particle/ambient interface with a rapidly decaying field distribution towards the center of the particle (cf. , e.g . , A. N . Oraevsky, Quant. Electron . Vol. 32, pp. 377-400, 2002) . Therefore, under suitable conditions, e.g . , by applying a su itable outer coating 3 of sufficient thickness, homogeneity, and transparency, WGMs may be excited and travel just inside this coating .
  • FPMs may be excited only in the core 1 of the particle, which is supposed ly free of any magnetizable material.
  • the way of excitation of optical cavity modes can then be chosen such that it supports low-loss mode excitation.
  • an evanescent-field coupling scheme may be applied .
  • the core may be doped with a suitable fluorescent material, which can be excited through the coating of magnetizable material on the core surface (according to scheme II of Fig . 2).
  • the fluorescent material can be distributed inside of the particle in such way that mode excitation with sufficiently low losses for their observation can be achieved.
  • core 1 and coating 3 may bear different fluorescent materials with different excitation and/or emission wavelength regimes, depending on the optical properties of the hybrid particle.
  • a fluorescent material in the core may be easier to excite from the outside of the particle and then excites the fluorescent material in the coating by means of its fluorescence emission , which in turn excites optical cavity modes, or vice versa, i.e. the fluorescence emission in the coating is easier to excite and then excites in turn that of the core for same purpose.
  • the coating 3 is chosen such that it facilitates excitation of optical cavity modes, such as WGMs, inside of the microresonator.
  • the core 1 contains a fluorescent material, which can be excited by means of suitable excitation light through the magnetizable material 2.
  • the wavelength of the excitation light can be chosen such that the magnetizable material 2 shows low absorption for this wavelength.
  • the core 1 is chosen such that optical cavity modes can be excited inside of the microresonator, e.g. FPMs.
  • the operable wavelength range can be chosen such that the magnetizable material 2 encapsulating the core 1 shows high reflectance, thereby promoting the occurrence of optical cavity modes inside of the core 1 .
  • the core 1 and the magnetizable material 2 are chosen such that optical cavity modes can be excited inside of the microresonator, e.g. FPMs.
  • the excitation and emission wavelength ranges of the fluorescent material can be chosen such that they fall into a window of low absorption of the magnetizable material 2.
  • the emission wavelength range of the fluorescent material in the core 1 may at least partially overlap the excitation wavelength range of the fluorescent material of the outer coating 3, and vice versa.
  • the magnetizable material 2 may also be borne by the outer coating 3.
  • the fluorescent materials of core 1 and outer coating 3 may differ from each other and differ from the magnetizable material 2.
  • microresonators and/or clusters of microresonators of the present embodiment can be manufactured by using materials, which are available to the public. The following explanations of the materials are provided to help those skilled in the art construct the microresonators and clusters of microresonators in line with the description of the present specification .
  • Cavity material Materials that can be chosen for fabrication of the cavity are those who exhibit low absorption in that part of the electromagnetic spectrum, in which the cavity shall be operated. In the case of fluorescence excitation, this is a region of the emission spectrum of the fluorescent material chosen for excitation of the cavity modes. In the case of evanescent field coupling , it is at least a part of the spectral range of the light source applied. In the case of clusters of microresonators or that more than a single microresonator is used in an experiment, the different cavities involved (either constituting the cluster or those of the different single microresonators) may be made from different materials and also may be doped with different fluorescent materials, e.g. to allow their selective excitation.
  • the cavity (cavities) may consist of heterogeneous materials.
  • the cavity (cavities) may bear a magnetizable material.
  • the magnetizable material (or any other material introduced for other kind of purpose or function of the cavity) may be distributed in a heterogeneous fashion throughout the cavity. For example, it may be distributed such that it does not distort the generation of those optical cavity modes, by which the cavity shall be operated, despite of potentially unfavorable optical properties, such as high refractive index, scattering cross-section, or absorption.
  • the cavity (cavities) is (are) made from semiconductor quantum well structures, such as InGaP/lnGaAIP quantum well structures, which can be simultaneously used as cavity material and as fluorescent material, when pumped with suitable radiation.
  • semiconductor quantum well structures such as InGaP/lnGaAIP quantum well structures
  • the typical high refractive index of semiconductor quantum well structures of about 3 and above further facilitates the miniaturization of the cavity or cavities because of the wavelength reduction inside of the semiconductor compared to the corresponding vacuum wavelength.
  • a photonic crystal as cavity material and to coat either the outer surface of the crystal with a fluorescent material, or to embed the fluorescent material into the crystal in a homogeneous or heterogeneous fashion.
  • a photonic crystal can restrict the number of excitable cavity modes, enforce the population in allowed modes, and define the polarization of the allowed modes.
  • the kind of distribution of the fluorescent material throughout the photonic crystal can further help to excite only the wanted modes, while unwanted modes are suppressed due to improper optical pumping.
  • the optical cavities shown have a spherical shape.
  • the cavity may in principle have any shape, such as oblate spherical shape, cylindrical, or polygonal shape given that the cavity can support cavity modes, as shown in the related art.
  • the shape may also restrict the excitation of modes into a single or a countable number of planes within the cavity volume.
  • Fluorescent material any type of material can be used that absorbs light at an excitation wavelength exc , and re-emits light subsequently at an emission wavelength ⁇ ⁇ ⁇ ⁇ . Thereby, at least one part of the emission wavelength range(s) should be located within the mode spectrum of the cavity for whose excitation the fluorescent material shall be used.
  • fluorescent dyes, semiconductor quantum dots, semiconductor quantum well structures, carbon nanotubes J . Crochet et al., Journal of the American Chemical Society, 129, pp. 8058-9, 2007
  • Raman emitters and the like can be utilized.
  • a Raman emitter is a material that uses the absorbed photon energy partially for excitation of internal vibrational modes and re-emits light with a wavelength higher than that of the exciting light. If a vibration is already excited , the emitted light may also have a smaller wavelength than the incoming excitation, thereby quenching the vibration (anti-Stokes emission). In any case, by proper choice of the excitation wavelength many non-metallic materials may show Raman emission , so that also the cavity materials as described above can be used for Raman emission without addition of a particular fluorescent material.
  • fluorescent dyes which can be used in the present invention are shown together with their respective peak emission wavelength (unit: nm): PTP (343), DMQ (360), butyl-PBD (363), RDC 360 (360), RDC 360-NEU (355), RDC 370 (370), RDC 376 (376), RDC 388 (388), RDC 389 (389), RDC 390 (390), QU I (390), BBD (378), PBBO (390), Stilbene 3 (428), Coumarin 2 (451 ), Coumarin 1 02 (480), RDC 480 (480/470), Coumarin 307 (500), Coumarin 334 (528), Coumarin 1 53 (544), RDC 550 (550), Rhodamine 6G (580), Rhodamine B (503/610), Rhodamine 101 (620), DCM (655/640), RDC 650 (665), Pyridin 1 (71 2/695), Pyridin 2 (740/720), Rhodamine 800 (810/798), and Styryl 9 (850/830).
  • any other dye operating in the UV-N IR regime could also and/or additionally be used.
  • fluorescent dyes are shown: DMQ, QUI, TBS, DMT, p-Terphenyl, TMQ, BPBD-365, PBD, PPO, p-Quaterphenyl, Exalite 377E, Exalite 392E, Exalite 400E, Exalite 348, Exalite 351 , Exalite 360, Exalite 376, Exalite 384, Exalite 389, Exalite 392A, Exalite 398, Exalite 404, Exalite 41 1 , Exalite 416, Exalite 41 7, Exalite 428, BBO, LD 390, a-NPO, PBBO, DPS, POPOP, Bis-MSB, Stilbene 420, LD 423, LD 425, Carbostyryl 165, Coumarin 440, Coumarin 4
  • Combinations of different dyes may be used, for example with at least partially overlapping emission and excitation regimes, for example to tailor or shift the operation wavelength regime(s) of the microresonator(s).
  • Water-insoluble dyes such as most laser dyes, are particularly useful for incorporation into the beads, while water-soluble dyes, such as the dyes obtainable from I nvitrogen (Invitrogen Corp. , Carlsbad , CA), are particularly usefu l for stain ing of the environment of the beads, including their surface.
  • Quantum dots that can be used as fluorescent materials for doping the microresonators have been described by Woggon and co-workers (M . V. Artemyev & U . Woggon , Applied Physics Letters 76, pp. 1 353-1 355, 2000; M . V. Artemyev et al. , Nano Letters 1 , pp. 309-314, 2001 ).
  • quantum dots CdSe, CdSe/ZnS, CdS, CdTe for example
  • Kuwata-Gonokami and co-workers M . Kuwata-Gonokami et al .
  • the excitation wavelength A exc of the fluorescent material does not have necessarily to be smaller than its emission wavelength em , i.e. ⁇ ⁇ ⁇ ⁇ , since one also can imagine multiphoton processes, where two or more photons of a given energy have to be absorbed by the material before a photon of twice or higher energy will be emitted . Also, as mentioned above, Raman anti-Stokes processes might be used for similar purpose.
  • Combinations of d ifferent fluorescent materials may be used , for example to tailor or shift the operation wavelength regime(s) of the optical cavity (cavities) or microresonator(s) . This may be achieved , for example, by suitable combination of excitation and emission wavelength regimes of the different fluorescent materials applied .
  • the fluorescent material can be incorporated into the cavity material, adsorbed on the cavities' or microresonators' su rface, and/or placed in the cavities' or microresonators' immediate environment, e.g . with in the evanescent field of the cavity modes to be excited .
  • the distribution can be used to select the type of cavity modes that are (preferably) excited . For example, if the fluorescent material is concentrated in vicinity of the core surface, whispering gallery modes are more likely to be excited than Fabry Perot modes. If the fluorescent material is concentrated in the centre of the cavity, Fabry Perot modes are easier to excite.
  • Other examples of a heterogeneous distribution are those, in which the fluorescent material is distributed in an ordered fashion , i .e.
  • the fluorescent material may further bear magnetic function , for example as is the case for transition metal-doped QDs or for fluorescently doped magnetizable material.
  • the latter may be ach ieved , for example, by decorating a magnetizable particle, such as a hematite or magnetite particle, with a fluorescent material, such as a fluorescent dye or QD(s).
  • the magnetizable material may be any suitable paramag netic, superparamagnetic, or ferromagnetic material, such as the transition metals, aluminum, and their composites. Further, any other kind of material doped with a a suitable paramagnetic, superparamag netic, and/or ferromagnetic material may be applied .
  • quantum dots doped with managanese may be used to provide wanted optical and magnetic properties simultaneously (D . Magana et al. , J . Am . Chem. Soc. Vol. 1 28, pp . 2931 -2939, 2006; L. Besombes et al. , Acta Phys. Polonica A, Vol . 1 08 , pp.
  • the mag netizable material may be introduced in form of particu lates or particles, continuous or contiguous films or coatings.
  • the mag netizable material may be further coated or fu nctionalized with other kinds of materials, such as fluorescent material(s) (bio-)functional material(s) to introduce wanted optical or (bio-)fu nctional properties, such as fluorescence, luminescence, specific binding capability, and/or resistance to non-specific bind ing .
  • the cavities and/or the clusters of cavities or microresonators might be embedded in a shell, which may have a homogeneous thickness or not.
  • the shell may be part of the optional coating 3 of the magnetic particles shown in Fig . 3, part of its core 1 , the magnetizable material 2, or may be additionally introd uced . It may bear magnetizable material and may consist of any material (metal, dielectric, semiconductor) that shows sufficient transmission at least in a part of the excitation wavelength reg ime(s) exc of the chosen fluorescent material(s) .
  • the shell may consist of d ifferent materials with wanted properties, for example to render the surface of microresonator(s) and/or cluster(s) of microresonators transparent only at wanted locations and/or areas or - to give another example - to facilitate selective (bio-)functionalization .
  • the shell bears a magnetizable material, it may located or distributed such that it does not distort other shell functions, such as its optical or (bio-)fu nctional properties or function(s) . I n the case of semiconductors, the shell becomes transparent when the excitation wavelength is higher than the wavelength corresponding to the bandgap of the considered semiconductor.
  • h igh transparency may be achieved , for example, by taking advantage of the plasma freq uency of the metal, above which the conduction electrons of the metal typically do no longer contribute to the absorption of electromagnetic radiation .
  • useful metals are aluminum and transition metals, such as silver, gold , copper, titanium, ch romium, cobalt and the like.
  • the shell can be continuous, as fabricated for example via evaporation or sputtering , or contiguous as often ach ieved by means of colloidal metal particle deposition and subsequent electroless plating (Braun & Natan , Langmuir 14, pp. 726- 728, 1 998; J i et al. , Advanced Materials 1 3, pp.
  • the th ickness of the shell may vary from a few nanometers to several h undreds of nanometers.
  • the only stringent requirement is that the reflectivity of the shell is sufficiently hig h in the wanted spectral range to allow for Q-factors with values of Q > 1 .
  • the Q-factor can be calculated from the reflectance of the shell 4 (or vice versa) by the formula [Math .5] m ⁇ (5)
  • Biofunctional coating The microresonator(s) or clusters of microresonators may be coated with a (bio-)functional coating facilitating their (bio-)mechanical and/or (bio-) chemical function. For example, they may be functionalized with specific analytes to initiate a wanted cell response, or to facilitate biomechanical and/or biochemical sensing.
  • the biofunctional coating may be part of the microresonator(s) shell or optional coating 3 of the magnetic particles shown in Fig . 3 or may be additionally introduced.
  • the biofunctional coating may - besides is biofunctional properties or function(s) - also bear optical or magnetic properties, at least temporally. This may also be achieved, for example, by use of optically (e.g. fluorescently or luminescently) and/or magnetizably labeled (bio-) molecules.
  • optically e.g. fluorescently or luminescently
  • bio- magnetizably labeled
  • the sensor surface With coupling agents that are capable of (preferably reversibly) binding an analyte, such as proteins, peptides, and nucleic acids.
  • analyte such as proteins, peptides, and nucleic acids.
  • Methods for conjugating coupling agents are well-known to those skilled in the art for various kinds of surfaces, such as polymers, inorganic materials (e.g. silica, glass, titania) and metal surfaces, and are equally suitable for derivatizing the sensor surface of the present invention.
  • a transition metal-coating e.g.
  • the senor of the present invention can be chemically modified by using thiol chemistries.
  • the metal-coated non-metallic cores can be suspended in a solution of thiol molecules having an amino group such as aminoethanethiol so as to modify the sensor surface with an amino group.
  • biotin modified with N-hydroxysuccinimide suspended in a buffer solution of pH 7 - 9 can be activated by EDC, and added to the sensor suspension previously modified by an amino group.
  • an amide bond is formed so as to modify the metal-coated non-metallic cores with biotin.
  • biotin or streptavidin comprising four binding sites can be bound to the biotin.
  • any biotin-derivatized biological molecule such as protein, peptide, DNA or any other ligand can be bound to the surface of the avidin-modified metal- coated non-metallic cores.
  • amino-terminated surfaces may be reacted with an aqueous glutardialdehyde solution. After washing the sensor suspension with water, it is exposed to an aqueous solution of proteins or peptides, facilitating covalent coupling of the biomolecules via their amino groups (R. Dahint et al. , Anal. Chem. , 1994, 66, 2888-2892). If the sensor is first carboxy-terminated , e.g.
  • sensors coated with other metals such as aluminum
  • non-metallic sensors can be specifically functionalized .
  • aluminum can be functionalized with molecules containing carboxyl groups, which then may serve as linker groups for further biofunctionalization in a similar fashion as the thiols discussed above.
  • Related kinds of chemistries for surface functionalization are available for a large range of metals, semiconductors, and their oxides.
  • suitable kinds of coupling agents such as amino-, mercapto-, hydroxy-, or carboxy-terminated siloxanes, phosphates, amines, carboxylic or hydroxamic acids, and the like, can be utilized for chemical functionalization of the sensor surface, on which basis then coupling of biomolecules can be achieved as described or in similar fashion as in the examples above.
  • Suitable surface chemistries can be found in the literature
  • PE polyelectrolytes
  • PSS PSS
  • PAA PAA
  • PAH PAH
  • a general problem in controlling and identifying biospecific interactions at surfaces and particles is non-specific adsorption .
  • Common techniques to overcome this obstacle are based on exposing the functionalized surfaces to other, strongly adhering biomolecules in order to block non-specific adsorption sites (e.g . to BSA).
  • BSA non-specific adsorption sites
  • the efficiency of this approach depends on the biological system under study and exchange processes may occur between dissolved and surface bound species.
  • the removal of non-specifically adsorbed biomolecules may require copious washing steps, thus, preventing the identification of specific binding events with low affinity.
  • a solution to this problem is the integration of the coupling agents into inert materials, such as coatings of poly- (PEG) and oligo(ethylene glycol) (OEG).
  • PEG poly-
  • OEG oligo(ethylene glycol)
  • the most common technique to integrate biospecific recognition elements into OEG-terminated coatings is based on co-adsorption from binary solutions, composed of protein resistant EG molecules and a second , functionalized molecular species suitable for coupling agent coupling (or containing the coupling agent itself).
  • binary solutions composed of protein resistant EG molecules and a second , functionalized molecular species suitable for coupling agent coupling (or containing the coupling agent itself).
  • Alternatively, also direct coupling of coupling agent to surface-grafted end-functionalized PEG molecules has been reported.
  • the binding entities immobilized at the surface may be proteins such as antibodies, (oligo-)peptides, oligonucleotides and/or DNA segments (which hybridize to a specific target oligonucleotide or DNA, e.g. a specific sequence range of a gene, which may contain a single nucleotide polymorphism (SN P), or carbohydrates).
  • proteins such as antibodies, (oligo-)peptides, oligonucleotides and/or DNA segments (which hybridize to a specific target oligonucleotide or DNA, e.g. a specific sequence range of a gene, which may contain a single nucleotide polymorphism (SN P), or carbohydrates).
  • SN P single nucleotide polymorphism
  • the sensors of the present invention may be utilized as remote sensors and therefore may require control of their positions and/or movements by external means, for example to control their contact and/or interaction with a selected target, such as a cell. Such control may be achieved by different means.
  • the sensors may be rendered magnetic and electromagnetic forces may be applied to direct the sensor(s) (C. Liu et al. , Appl. Phys. Lett. Vol. 90, pp. 184109/1 -3, 2007).
  • paramagnetic and super-paramagnetic polymer latex particles containing magnetic materials, such as iron compounds are commercially available from different sources (e.g.
  • Magnetic material is embedded into a polymeric matrix material, which is typically made of polystyrene, such particles may be utilized in the same or a similar way as optical cavity mode sensors as the non-magnetic PS beads described in the examples below.
  • a magnetic material/functionality may be borne by the shell of the microresonator(s) and/or their (bio-)functional coating.
  • the position control may be mediated by means of optical tweezers (J. R. Moffitt et al., Annu. Rev. Biochem. Vol. 77, pp. 205-228, 2008).
  • the laser wavelength(s) of the optical tweezers may be either chosen such that it does or that it does not coincide with excitation and/or emission wavelength range(s) of the fluorescent material(s) used to operate the sensor.
  • One advantage of optical tweezers over magnetic tweezers would be that a number of different sensors may be controlled individually at the same time (C. Mio et al., Rev. Sci. Instr. Vol. 71 , pp. 21 96- 2200, 2000).
  • position and/or motion of the sensors may be controlled by acoustic waves (M . K. Tan et al., Lab Chip Vol. 7, pp. 618-625, 2007), (di)electrophoresis (S. S. Dukhin and B. V. Derjaguin, "Electrokinetic Phenomena”, John Wiley & Sons, New York, 1 974; H . Morgan and N . Green, “AC Electrokinetics: colloids and nanoparticles", Research Studies Press, Baldock, 2003; H . A. Pohl, J. Appl. Phys. Vol. 22, pp. 869-671 , 1951 ), electrowetting (Y. Zhao and S. Cho, Lab Chip Vol. 6, pp.
  • microfluidics device that potentially may also be capable of sorting/picking particles and/or cells of desired dimension and/or fu nction (S . Hardt, F. Schonfeld , eds. , "M icrofluidic Technologies for Min iaturized Analysis Systems", Springer, New York, 2007).
  • mechanical tweezers may be utilized for position control of the sensor(s) , for example by employing a microcapillary capable of fixing and releasing a particle via application of pressure differences (M . Herant et al. , J . Cell Sci. Vol. 1 1 8 , pp. 1 789-1 797, 2005).
  • M Herant et al.
  • sensors and cells may be manipulated using the same instrumentation (cf. M . Herant et al.) .
  • combinations of two or more of the schemes described above may be suitable for position control of sensor(s) and/or target(s) .
  • Excitation light source The choice of light source for optical cavity mode excitation depends on the excitation scheme applied .
  • the emission wavelength range should match the wanted spectral regime of operation of the cavity.
  • the light source For excitation via fluorescence emission , the light source has to be chosen such that its emission falls into the excitation frequency range co exc of the fluorescent material.
  • the emission power should be such that it can overcompensate the losses (rad iation losses, damping , absorption , scattering) that may occur in the course of excitation of the microcavity or cluster of microcavities.
  • thermal sources such as tungsten or mercu ry lamps may be applied .
  • Lasers or high power light emitting d iodes with their narrower emission profiles will be preferably applied to min imize heating of sample and environment.
  • a narrow-band tu nable light source may be applied to facilitate the detection of optical cavity modes, e.g . , in the case of the evanescent field coupling scheme. If several fluorescent materials are utilized with properly chosen, e.g. non- overlapping , excitation frequency ranges, more than a single light source or a sing le lig ht source with switchable emission wavelength range may be chosen such that ind ividual microcavities or clusters of microcavities may be addressed selectively, e.g .
  • a fluorescent microcavity may be operated above the threshold for stimulated emission of the cavity.
  • the bandwidths of the operating cavity modes will further narrow, thus improving their quality factors (M. Kuwata-Gonokami et al. , Jpn. J. Appl. Phys. (Part 2) Vol. 31 , pp. L99ff.). This kind of operation will be particularly useful for the basic schemes of Sections 4.2.1 -3.
  • preferred light sources are thermal sources, such as tungsten and mercury lamps, and non-thermal sources, such as gas lasers, solid-state lasers, laser diodes, DFB lasers, and light emitting diodes (LED).
  • thermal sources such as tungsten and mercury lamps
  • non-thermal sources such as gas lasers, solid-state lasers, laser diodes, DFB lasers, and light emitting diodes (LED).
  • a LED can be preferably chosen such that its emission falls at least partially into the excitation frequency range exc of (at least one of) the fluorescent material(s) applied.
  • the emission power should be such that it can overcompensate the losses (radiation losses, damping , absorption , scattering) that may occur in the course of excitation of the microresonators. If several fluorescent materials are utilized with suitably chosen, e.g.
  • non-overlapping or partially overlapping, excitation frequency ranges more than a single LED may be chosen such that individual microresonators or clusters of microresonators may be addressed selectively, e.g. to further facilitate the readout process or for the purpose of reference measurements. For example, it may be desirable to address only a single microresonator within a cluster. Further, the excitation power of at least one of the LEDs may be chosen such that at least one of the microresonator(s) or cluster(s) of microresonators utilized is/are operated - at least temporally - above the lasing threshold of at least one of the optical cavity modes excited.
  • Optical detection of optical cavity modes depends on the excitation scheme applied. In the case of an evanescent field coupling scheme, the loss in the excitation light may be monitored as known to those skilled in the art (cf. , e.g. , F. Vollmer et al. , Appl. Phys. Lett. Vol. 80, pp. 4057ff. , 2002). Alternatively, light emitted or scattered from the microcavity (microcavities) or (a) cluster(s) thereof may be spectrally analyzed by means of one or more dispersive, e.g .
  • the emitted or scattered light may be collected by means of any kind of light collection optics known to those skilled in the art.
  • the emission can be collected by a microscope objective of suitable numerical aperture and/or any other kind of suitable far-field optics, by an optical fiber, a waveguide structure, an integrated optics device, the aperture of a near field optical microscope (SNOM), or any suitable combination thereof.
  • the collection optics may utilize far-field and/or near-field aspects for detection of the signal.
  • the collected light can be analyzed by any kind of suitable spectroscopic apparatus based on diffractive and/or interferometric elements.
  • the direct interference of the emitted or scattered light may be analyzed, e.g., by means of interference patterns recorded by a CCD camera or other kind of spatially resolving detector.
  • confocal fluorescence microscopes combine fluorescence excitation via laser light with collection of the fluorescence emission with high numerical aperture, followed by filtering and spectral analysis of the fluorescence emission. Since such instruments are often used in biochemical and biological studies, they may provide a convenient tool for implementation of the present invention.
  • Other convenient instruments are, for example, Raman microscopes, which also combine laser excitation and high numerical aperture collection of light signals from microscopic sources with spectral analysis.
  • both kinds of instruments allow simultaneous spectral analysis and imaging, which facilitates tracing of the microresonator position(s) in the course of their operation. If such imaging information is not required, also other kinds of devices, such as fluorescence plate readers, may be applicable.
  • optical microcavity bearing a magnetizable material, wherein the microcavity can (freely) move in a suitable medium, such as a fluid, and its position may be controlled - at least temporally - by magnetization of its magnetizable material through external magnetic forces, e.g. , by magnetic tweezers.
  • the optical microcavity can be used for different purposes, e.g. to deliver light generated by means of optical cavity mode excitations in its interior to a wanted location . Also, it can be used to mediate a process of optical sensing at a wanted location or between wanted locations. According to other applications of optical microcavities (cf.
  • the microcavity may serve one or more purposes at one location and the same or other purposes at another location.
  • a cluster of optical cavities or microresonators wherein at least one of the optical cavities or microresonators is an optical microcavity bearing a magnetizable material.
  • the cluster can (freely) move in a suitable medium, such as a fluid , and its position may be controlled - at least temporally - by magnetization of its magnetizable material through external magnetic forces, e.g ., by magnetic tweezers.
  • the cluster or at least one of its constituting optical cavities or microresonators can be used for different purposes, e.g . to deliver light generated by means of optical cavity mode excitations in its interior to a wanted location . Also, the cluster or at least one of its
  • the cluster or at least one of its constituents can be further used as laser(s), optical filters, switches, and modulators at the wanted location .
  • This location may be changed in the course of the application of the cluster as well as the purpose of using the cluster may be altered.
  • the cluster may serve one or more purposes at one location and the same or other purposes at another location.
  • a cluster of optical microcavities which bear a magnetizable material.
  • the magnetizable material of different optical microcavities may be different.
  • the cluster forms from its constituent optical microcavities by application of magnetic forces.
  • the individual microcavities may freely float in a fluid, e.g . , in the course of a sensing process, e.g . , for collection of a wanted analyte.
  • After switching of magnetic forces for example: on, off, increase, decrease, alternating field, varying field, alternating field with DC offset
  • the individual optical microcavities assemble to form the cluster. This process may be reversible and may depend on the applied magnetic field(s).
  • An optical microcavity or cluster thereof which interacts with a magnetized material in its environment via magnetic forces.
  • the optical microcavity or cluster thereof may move or rest. For example, it may rest on a surface.
  • the interaction with the magnetized material may help or be part of a sensing process applying optical cavity mode excitations as (one of) the transducer mechanism(s).
  • the interaction with the magnetized material may alter the kinetics and/or sensitivity of the sensing process. For example, it may help the specificity of a specific sensing process, for example by suppression of non-specific binding and/or by supporting specific binding. For example, it may kinetically favour a wanted sensing process. Such and related function may be facilitated, for example, by application of
  • magnetizable particles attached to or incorporated into a wanted material.
  • This example shows how a single magnetite crystallite with a th ickness of only 1 0 nm can ruin the Q-factor of an optical cavity mode with a trajectory through the crystallite.
  • n n + i K (6)
  • ⁇ 0 is the vacuum wavelength of consideration. For example, for a photon energy of 2 eV, ⁇ 0 « 620 nm.
  • the bandwidths of the fluorescence emission of a typical fluorescent material applied for optical cavity mode operation is typically in the range of a few tens (for most QDs) to several tens (for most organic dyes) of nanometers.
  • the bandwidth of the mode would become comparable to or even larger than that of the overall fluorescent background of the fluorescent material and thus would no longer be discernible.
  • This example shows how fluorescently doped superparamagnetic beads can be prepared from commercially available superparamagnetic polymer beads.
  • a magnetic stirrer is applied, which is, however, not applicable in the case of paramagnetic beads, because it would cause the aggregation of the beads in vicinity of the stirrer, thereby hindering their contacts with the dye
  • a non-magnetic stirrer as sketched in Fig. 2 was set up and applied to the inking process of 8 ⁇ Compel paramagnetic polystyrene beads from Bangs, Laboratories, Inc. , Fishers, IN.
  • a brass gear wheel 1 of about 1 3 mm outer diameter bearing 24 cogs of about 1 .25 mm length is mounted to a shaft 5, which in turn is connected via a coupler 6 to the shaft of a DC micromotor 7 (Model HS-GM21 -ALG, S.T.L. Japan) with electric contacts 8.
  • the contacts 8 are connected to a suitable power supply to drive the motor (0.7 - 7.2 V DC).
  • the motor further contains a gearbox, which reduces the motor speed from 4500-14,250 rpm to 60-1 90 rpm depending on the voltage setting and is fixed to a mechanical holder 9 in such way, that a beaker 4 can be placed underneath the motor 7 and the gear wheel 1 can be positioned about 10-20 mm above the inner bottom of the beaker 4.
  • an additional bearing 1 0 made of Nylon is placed just above the beaker for and fixed to the
  • the beaker is first filled with a highly diluted suspension 2 (150 mL native bead suspension in 1 0ml_ deionized water) of superparamagnetic microspheres (Compel paramagnetic beads, nominal diameter 8 ⁇ , 5 wt% solids contents, catalog code UMC4N, LOT 861 0, Bangs Laboratories, Inc., Fishers, IN), then a saturated NR/xylene solution 3 is carefully placed on top of the aqueous suspension to form the aforementioned two-phase system.
  • the power supply was set to 5 V DC, resulting in a moderate speed of the gear wheel 1 due to some friction of the shaft 5 in the bearing 1 0.
  • Microspheres In this example, we demonstrate that optical cavity modes with WGMs as the example can be generated in fluorescent superparamagnetic polymer beads despite the presence of the strongly absorbing and scattering magnetic material.
  • Materials & Methods A drop of suspension of NR-doped superparamagnetic microbeads as prepared according to Example 1 with a nominal diameter of 8 ⁇ was placed on a glass microscopy cover slip. The sample was mounted onto the sample stage of a Nikon TS100 inverted microscope, which was used for observation and selection of suitable microbeads as well as their excitation and detection. For excitation, a picosecond Nd:YAG laser (Model Rapid, Lumera Lasers, Germany) operated at 532 nm was applied.
  • the laser power at the microscope objective used for excitation and detection was 24.7 ⁇ with a focus of about 20 ⁇ .
  • the light was guided through the camera port of the microscope to the entrance slit of a high-resolution monochromator (Horiba Yobin-lvon Triax 550, 600 L/mm grating, width of entrance slit 10 ⁇ ) equipped with a cooled CCD camera (Andor Technologies, Harbor, model DU-440 BU). Acquisition settings were 1 s exposure time, 20 accumulations.
  • Fig . 3 displays two spectra (a) and (b), which were obtained from two different microbeads, the first spectrum (a) from a NR-doped microbead, thereby allowing the excitation of optical cavity modes, the second spectrum (b) from a microbead of the native, i.e. non-fluorescent superparamagnetic bead suspension.
  • the doped bead shows very nice WGM excitation as that known from the prior art for particles in this size regime (cf. , e.g. , A. Francois and M. Himmelhaus, Sensors Vol. 9, pp. 6836- 6852, 2009), while the non-doped particle does not show any fluorescence emission at all. While this could be expected, there was some concern if the supposedly strong absorption of the picosecond laser excitation by the brownish beads might cause some unexpected effects. Obviously, this is not the case, however.

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Abstract

Un appareil à modes de cavité optique comprend au moins une microcavité présentant un certain magnétisme ; une source lumineuse destinée à faire bénéficier la microcavité d'une exposition à la lumière ; un appareil optique servant à la détection des modes de cavité optique de la microcavité ; et un dispositif de commande magnétique permettant de contrôler par voie magnétique la position de la microcavité.
PCT/JP2011/062859 2010-06-04 2011-05-30 Excitations des modes de cavité optique dans des microparticules magnétiques fluorescentes WO2011152543A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP11789943.5A EP2577276A4 (fr) 2010-06-04 2011-05-30 Excitations des modes de cavité optique dans des microparticules magnétiques fluorescentes
JP2012554140A JP2013527428A (ja) 2010-06-04 2011-05-30 磁気蛍光性微小粒子における光学的キャビティモード励起
US13/701,209 US20130105709A1 (en) 2010-06-04 2011-05-30 Optical Cavity Mode Excitations in Magnetic Fluorescent Microparticles

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Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2589618B2 (ja) * 1989-12-14 1997-03-12 デイド、インターナショナル、インコーポレイテッド 磁気応答性螢光ポリマー粒子及びその利用
WO2001015288A1 (fr) 1999-05-17 2001-03-01 New Mexico State University Technology Transfer Corporation Amelioration optique au moyen de nanoparticules et de microcavites
WO2002001147A1 (fr) 2000-06-28 2002-01-03 The Charles Stark Draper Laboratory, Inc. Capteur chimique comportant un resonateur a microcavite optique revetue
WO2002013337A1 (fr) 2000-08-08 2002-02-14 California Institute Of Technology Detection optique basee sur une microcavite a mode de galerie
WO2002071013A1 (fr) 2001-03-01 2002-09-12 New Mexico State University Technology Transfer Corporation Dispositifs et procedes optiques utilisant des nanoparticules, des microcavites et des films metalliques en semi-continu
US20030206693A1 (en) 2001-06-28 2003-11-06 Tapalian Haig Charles Optical microcavity resonator sensor
US20030218744A1 (en) 2000-09-19 2003-11-27 Shalaev Vladimir M. Optical structures employing semicontinuous metal films
WO2004038349A1 (fr) 2002-10-24 2004-05-06 Purdue Research Foundation Analyse optique assistee par plasmonique et/ou par microcavites
US20040150818A1 (en) 1999-05-17 2004-08-05 Armstrong Robert L. Optical devices and methods employing nanoparticles, microcavities, and semicontinuous metal films
US20050022153A1 (en) 2003-07-22 2005-01-27 Yih-Feng Hwang Integration of information distribution systems
WO2005116615A1 (fr) 2004-05-26 2005-12-08 Genera Biosystems Pty Ltd Biodetecteur utilisant des modes de voute acoustique dans des microspheres
JP2007169261A (ja) * 2005-12-23 2007-07-05 Ind Technol Res Inst 特異的標的機能を有する蛍光磁気ナノ粒子
WO2007129682A1 (fr) 2006-05-01 2007-11-15 Fujirebio Inc. Particules non métalliques fluorescentes encapsulées dans un revêtement métallique
JP2008528973A (ja) * 2005-01-20 2008-07-31 ルミネックス・コーポレーション 蛍光ベースの応用で使用される磁性ミクロスフェア
WO2008116093A2 (fr) * 2007-03-20 2008-09-25 Becton, Dickinson And Company Dosages utilisant des particules actives en spectroscopie raman amplifiée en surface (sers)
WO2009084721A1 (fr) * 2007-12-31 2009-07-09 Fujirebio Inc. Groupes de microrésonateurs pour une détection optique en mode cavité
JP2010008247A (ja) * 2008-06-27 2010-01-14 Fujifilm Corp 検出方法、検出装置、検出用試料セルおよび検出用キット
US11136908B2 (en) 2017-06-23 2021-10-05 Hs Marston Aerospace Limited Heated lubrication circuit

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010024466A1 (fr) * 2008-08-31 2010-03-04 Fujirebio Inc. Appareil et procédé d’analyse des modes de cavité optique

Patent Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2589618B2 (ja) * 1989-12-14 1997-03-12 デイド、インターナショナル、インコーポレイテッド 磁気応答性螢光ポリマー粒子及びその利用
WO2001015288A1 (fr) 1999-05-17 2001-03-01 New Mexico State University Technology Transfer Corporation Amelioration optique au moyen de nanoparticules et de microcavites
US20040150818A1 (en) 1999-05-17 2004-08-05 Armstrong Robert L. Optical devices and methods employing nanoparticles, microcavities, and semicontinuous metal films
WO2002001147A1 (fr) 2000-06-28 2002-01-03 The Charles Stark Draper Laboratory, Inc. Capteur chimique comportant un resonateur a microcavite optique revetue
WO2002013337A1 (fr) 2000-08-08 2002-02-14 California Institute Of Technology Detection optique basee sur une microcavite a mode de galerie
US20020097401A1 (en) 2000-08-08 2002-07-25 Luftollah Maleki Optical sensing based on whispering-gallery-mode microcavity
US20030218744A1 (en) 2000-09-19 2003-11-27 Shalaev Vladimir M. Optical structures employing semicontinuous metal films
WO2002071013A1 (fr) 2001-03-01 2002-09-12 New Mexico State University Technology Transfer Corporation Dispositifs et procedes optiques utilisant des nanoparticules, des microcavites et des films metalliques en semi-continu
US20030206693A1 (en) 2001-06-28 2003-11-06 Tapalian Haig Charles Optical microcavity resonator sensor
WO2004038349A1 (fr) 2002-10-24 2004-05-06 Purdue Research Foundation Analyse optique assistee par plasmonique et/ou par microcavites
US20050022153A1 (en) 2003-07-22 2005-01-27 Yih-Feng Hwang Integration of information distribution systems
WO2005116615A1 (fr) 2004-05-26 2005-12-08 Genera Biosystems Pty Ltd Biodetecteur utilisant des modes de voute acoustique dans des microspheres
JP2008528973A (ja) * 2005-01-20 2008-07-31 ルミネックス・コーポレーション 蛍光ベースの応用で使用される磁性ミクロスフェア
JP2007169261A (ja) * 2005-12-23 2007-07-05 Ind Technol Res Inst 特異的標的機能を有する蛍光磁気ナノ粒子
WO2007129682A1 (fr) 2006-05-01 2007-11-15 Fujirebio Inc. Particules non métalliques fluorescentes encapsulées dans un revêtement métallique
JP2009535604A (ja) * 2006-05-01 2009-10-01 富士レビオ株式会社 金属コーティングにてカプセル化された非金属蛍光粒子
WO2008116093A2 (fr) * 2007-03-20 2008-09-25 Becton, Dickinson And Company Dosages utilisant des particules actives en spectroscopie raman amplifiée en surface (sers)
WO2009084721A1 (fr) * 2007-12-31 2009-07-09 Fujirebio Inc. Groupes de microrésonateurs pour une détection optique en mode cavité
JP2010008247A (ja) * 2008-06-27 2010-01-14 Fujifilm Corp 検出方法、検出装置、検出用試料セルおよび検出用キット
US11136908B2 (en) 2017-06-23 2021-10-05 Hs Marston Aerospace Limited Heated lubrication circuit

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
A. FRANCOIS; M. HIMMELHAUS, APPL. PHYS. LETT., vol. 92, 2008, pages 141107,1 - 3
A. FRANCOIS; M. HIMMELHAUS, APPL. PHYS. LETT., vol. 94, 2009, pages 031101
A. FRANCOIS; M. HIMMELHAUS, APPL. PHYS., vol. 94, 2009, pages 031101,1 - 3
A. FRANCOIS; M. HIMMELHAUS, BIOSENS. BIOELECTRON., vol. 25, 2009, pages 418 - 427
A. N. ORAEVSKY, QUANT. ELECTRON., vol. 32, 2002, pages 377 - 400
A. WELLER ET AL., APPL. PHYS. B, vol. 90, 2008, pages 561 - 567
F. VOLLMER; S. ARNOLD, NATURE METHODS, vol. 5, 2008, pages 591 - 596
MICHAEL HIMMELHAUS ET AL.: "In-vitro sensing of biomechanical forces in live cells by a whispering gallery mode biosensor", BIOSENSORS AND BIOELECTRONICS, vol. 25, 2009, pages 418 - 427, XP026600444 *
N. LE THOMAS ET AL., J. OPT. SOC. AM. B, vol. 23, 2006, pages 2361 - 2365
P. SHASHANKA ET AL., OPT. EXPRESS, vol. 14, 2006, pages 9460 - 9466
See also references of EP2577276A4
T. MUKAIYAMA ET AL., PHYS. REV. LETT., vol. 82, 1999, pages 4623 - 4626

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